张莉等

[摘要] 目的 分析济南军区总医院（以下简称“我院”）药物临床试验不良事件监测的方案设计现状，推动不良事件监测方案的规范化设计。 方法 调查我院2007～2013年Ⅱ～Ⅲ期项目的试验方案，对照不良事件的方案设计质量评分标准，分析不良事件设计质量的年均得分及各要素的年均得分率。并统计2012～2013年项目的不良事件设计质量中各要素的得分率以及各要素得分点的缺失率。 结果 我院药物临床试验不良事件监测的方案设计质量得分及各要素得分率均逐年提高。2012～2013年项目方案中，仍存在不良事件监测的关键信息设计缺失，其中缺失率>50%的得分点包括：妊娠事件、非不良事件的特殊事宜说明、不良事件的监测时间段、实验检查值的临床意义判定标准、不良事件与试验药物关联性评价方法、重要不良事件及导致受试者退出不良事件的报告要求、不良事件的源文件记录要求。 结论 试验方案中完善而周全的不良事件监测计划的制订是项目安全性评价质量的重要保证。通过对不良事件监测计划的各步骤细节进行探讨，提出不良事件监测方案的规范化设计。

[关键词] 药物临床试验；不良事件；设计质量

[中图分类号] R95 [文献标识码] A [文章编号] 1673-7210（2015）02（b）-0156-05

[Abstract] Objective To analyze design quality of adverse events monitoring in clinical drug trial of Ji'nan Military General Hospital （“our hospital” for short） and to promote normalization design of adverse events protocol. Methods The Ⅱ-Ⅲ period clinical drug trial protocol from 2007 to 2013 in our hospital was investigated， in comparison with score criterions of design quality for adverse events， the average scores per year and the score rate of items were analyzed. In addition， the score rate of items and the missing rate of each score point from 2012 to 2013 clinical drug trial protocol were also analyzed. Results The design quality score of adverse events in clinical drug trial protocol of our hospital， as well as the score rate of items， increased year by year. However， there were still some defects in 2012-2013 clinical drug trial protocol. The missing score point of design items， with the missing rate more than 50%， were shown as follows： pregnancy events， exclusions of adverse events， monitoring time of adverse events， criteria for clinical significance of experimental test value， the methods of association evaluation between adverse events and trail drugs， reporting requirements of significant adverse events and adverse events which caused the withdraw of subjects， the source file record requirements. Conclusion Establishing of a complete and comprehensive monitoring plan of adverse events in protocol is an important guarantee for assessment guality of project safety. By the discussion in details to each step of adverse events monitoring plan， normalization design of adverse events monitoring protocol is proposed.

[Key words] Clinical drug trial； Adverse events； Design quality

药物安全性一直是药物研发过程乃至上市后的临床运用中人们关注的重要问题。临床试验中监督试验药物的安全性是临床试验最重要的目标之一。不良事件的监测及管理是药物安全性评价的重要组成部分，原国家食品药品监督管理局于2003年发布了《药物临床试验质量管理规范》（GCP）[1]，从试验方案的设计、实施和记录等各方面对规范不良事件的监测和管理做出了明确的规定。